Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform

Definition:

PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase. Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53. Activates RAF1 by dephosphorylating it at 'Ser-259'. Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint. Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC. Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3.

References:

[1]. Feng Li, et al. CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication Stress. Mol Cell. 2020 Nov 5;80(3):410-422.e6. [Content Brief]

[2]. D Abraham, et al. Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation. J Biol Chem. 2000 Jul 21;275(29):22300-4. [Content Brief]

[3]. Juliane Becher, et al. AMBRA1 Controls Regulatory T-Cell Differentiation and Homeostasis Upstream of the FOXO3-FOXP3 Axis. Dev Cell. 2018 Dec 3;47(5):592-607.e6. [Content Brief]

[4]. Heng-Hong Li, et al. A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. EMBO J. 2007 Jan 24;26(2):402-11. [Content Brief]

[5]. W Hsu, et al. Identification of a domain of Axin that binds to the serine/threonine protein phosphatase 2A and a self-binding domain. J Biol Chem. 1999 Feb 5;274(6):3439-45. [Content Brief]

[6]. Valentina Cianfanelli, et al. AMBRA1 links autophagy to cell proliferation and tumorigenesis by promoting c-Myc dephosphorylation and degradation. Nat Cell Biol. 2015 Jan;17(1):20-30. [Content Brief]

[7]. Guy R Watkins, et al. Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit α4, altering PP2A stability and microtubule-associated protein phosphorylation. J Biol Chem. 2012 Jul 13;287(29):24207-15. [Content Brief]

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